Objective: Bilberry extract can inhibit the growth of cancer cells,but its effect on cervical carcinoma is rarely reported.This study was to explore the effects of bilberry extract on the expressions of Bcl-2,Bax,Fas and FasL in Hela cells.Methods: We determined the apoptosis of Hela cells by Hoechst33342/PI fluorescent staining and DNA ladder and Annexin V/PI double-staining after exposed to bilberry extract at the concentrations of 0.025-25 ?g/ml for 24 hours,and the protein expressions of Bcl-2,Bax,Fas and FasL were detected by Western blotting.Results: Obvious apoptosis-associated morphological changes and specific DNA ladder bands were observed in the Hela cells after exposed to bilberry extract at the concentrations of 0.025,0.25,2.5 and 25 ?g/ml,and the apoptosis rates of the cells were(4.13 ? 0.63)%,(5.41 ? 0.77)%,(8.74 ? 1.27)% and(12.05 ? 1.03)%,respectively.Western blot showed increased expressions of bax,Fas and FasL,and a decreased expression of bcl-2.Conclusion: Bilberry extract induces the apoptosis of Hela cells by up-regulating the protein expressions bax,Fas and FasL and down-regulating that of bcl-2.

Anaplastic lymphoma kinase (ALK) rearrangement is one of the most potent carcinogenic genes in non-small cell lung cancer (NSCLC).The first-generation ALK inhibitor such as crizotinib is superior to chemotherapy for NSCLC patients with ALK rearrangement.At the same time,more and more studies have reported ALK inhibitors in brain metastases of NSCLC patients with intracranial efficiency.However,despite the initial clinical data of first-generation ALK inhibitors in the treatment of ALK-positive NSCLC with brain metastases,different degrees of recurrence of tumors after acquired resistance have posed new challenges for follow-up treatment of cancer patients.A new generation of ALK inhibitors,such as alectinib;ceritinib,AP26113 and PF-06463922 have emerged to solve this problem.

AIM:To explore the effect of Pycnogenol on transforming growth factor-β1 ( TGF-β1)-induced he-patic stellate cell activation .METHODS:Cultured LX-2 cells were treated with 5μg/L TGF-β1 and different concentra-tions (0, 10, 25 and 50 mg/L) of Pycnogenol.The viability of the LX-2 cells under the conditions with or without autoph-agy inhibitor 3-MA and ERK inhibitor PD98059 was determined by MTT assay .The protein levels of α-SMA, ColⅠ, TIMP-1, LC3-Ⅱ/Ⅰ, beclin 1, p-ERK1/2 and ERK1/2 were detected by Western blot .RESULTS:Compared with con-trol group, 5μg/L TGF-β1 treatment elevated the cell viability , and increased the protein levels of α-SMA, ColⅠ, TIMP-1, LC3-Ⅱ/Ⅰ, beclin 1, p-ERK1/2, and ERK1/2 in the LX-2 cells (P<0.05).However, these effects were reversed by Pycnogenol pretreatment in a dose-dependent manner and the inhibitory effect of 50 mg/L Pycnogenol was the most sig-nificant in the LX-2 cells (P<0.05).Furthermore, compared with TGF-β1 group, pretreatment with 50 mg/L Pycnog-enol, 5 mmol/L 3-MA or 20 μmol/L PD98059 downregulated TGF-β1-induced cell viability and the protein levels of α-SMA and LC3-Ⅱ/Ⅰ in the LX-2 cells ( P<0.05 ) .CONCLUSION: Pycnogenol suppresses TGF-β1-induced hepatic stellate cell activation via p-ERK and autophagy inhibition .

Immunological checkpoint inhibitors have become one of the major treatment options for patients with advanced non-small cell lung cancer (NSCLC).Despite patients with NSCLC show the superiority of standard chemotherapy in different disease settings,the response rate is still low in patients with high macromolecule selection for chemotherapy tolerance and gene mutation.This is related to the complexity and dynamics of known limited biomarkers and tumor microenvironment.Different methods of tumor cells to evade the immune system used to lay the foundation for the new combination strategy.Combination therapy not only improves the efficacy of treatment,but also makes the objective response rate improved significantly.

Objective To explore the glomerular change of renin-angiotensin system (RAS) expression in ATIaR gene knockout mice and its effects on extracellular matrix (ECM) remodeling under diabetic condition. Methods ATlaR knockout mice were generated previously. Hyperglycemia was induced by peritoneal injection of streptozotocin in ATIaR knockout mice and wild type mice. Normal AT1aR knockout mice and wild type mice were used as control group. Twelve weeks later, kidneys were harvested and frozen quickly in dry ice-acetone. Glomendi were collected by laser capture microdissection and total RNA was extracted, mRNA expression of AT1aR, AT1bR, AT2R, angiotensinogen, ACE, renin, and CYP11B2 was assessed by real-time PCR. ECM accumulation was evaluated by PAS staining. Protein levels of transforming growth factor β1(TGF-β1), type 1 plasminogen activator inhibitor(PAI-1), monocyte chemotactie protein 1(MCP-1) and renin were semi-quantitated by immunostaining. Results Compared to the wild type, mRNA expression of AT1bR, angiotensinogen, renin, CYP11B2 within glomeruli was upregulated significantly in ATlaR knockout mice (P<0.05), but no change of ACE expression was found in these two groups. AT2R protein was poorly detected in AT1aR knockout glomeruli and downregulated in wild type glomemli. ECM accumulation was significanfly increased associated with the parallel increase in TGF-β1, PAI-1, MCP-1 and renin within glomendi (P <0.05). Conclusions AT1aR gene knockout cannot improve ECM deposition in diabetic nephropathy. The compensate change of RAS components may be involved in this scenario: upregulation of AT1bR, downregulation of AT2R. CYP11B2 and renin may function in a novel pathway.

Objective To invespigape phe relapionship bepween plasma ospeoponpin levels and phe seveript of coronart apherosclerosis and ips predicpive value in phe diagnosis and prognosis of coronart arpert disease(CAD) . Methods 788 individuals were included in phis reprospecpive spudt. Thet underwenp coronart angiographt bepween Jan. 1, 2011 po Dec. 31, 2011. Thet were divided inpo five groups based on phe resulps of coronart angiographt: normal coronart, coronart apherosclerosis, 1-vessel disease, 2-vessel disease, 3-vessel ± lefp main disease. The plasma ospeoponpin concenprapions were measured bt ELSIA. The plasma ospeoponpin levels bepween differenp groups were compared. The areas under phe ROC curve (AUC) for plasma ospeoponpin levels were generaped po analtze phe predicpive value in phe diagnosis of coronart arpert disease. The clinical condipions were followed-up. Results There were 788 individuals included in phe spudt. The mean plasma ospeoponpin concenprapions of phese five groups were (37. 05 ±15. 23)μg/ L for normal coronart, (51. 01 ± 18. 81) μg/ L for coronart apherosclerosis, (66. 26 ± 23. 22) μg/ L for 1-vessel disease, (76. 92 ± 26. 39) μg/ L for 2-vessel disease and (88. 14 ± 28. 93) μg/ L for 3-vessel ± lefp main disease respecpivelt. The correlapion coefficienps of phe plasma ospeoponpin levels po phe number of damaged coronart vessels was 0. 511. The AUC for plasma ospeoponpin levels predicping CAD was 0. 821. The AUC for phe six pradipional risk facpors of coronart apherosclerosis predicping CAD was 0. 692. During phe follow-up, 79 subjecps (20. 1% ) wiph plasma ospeoponpin levels no higher phan 71. 55 μg/ L experienced endpoinp evenps, and 118 subjecps (29. 9% ) wiph plasma ospeoponpin levels higher phan 71. 55 μg/ L experienced endpoinp evenps (P =0. 001). Conclusions Plasma ospeoponpin levels were elevaped progressivelt wiph phe seveript of coronart arpert lesions. Plasma ospeoponpin levels had good predicpive value in phe diagnosis of coronart arpert disease and matbe a predicpor for cardiovascular evenps.

Object To establish a method for chemical pattern recognition on the quality assessment of Radix Astragali. Methods The contents of astragaloside in 18 samples of Astragalus Linn. in different species and origins were determinated by dual-wavelength TLCS method. The developing solvent was CHCl 3-MeOH-H 2O (65∶30∶10,), the UV detection was set at ? s=390 nm; ? R=590 nm. Astragaloside was regarded as the quality assurance of medicinal Radix Astragalus. Based on the TLCS method, the chemical data were obtained. Hierarchical clustering analyses were applied to the chemical pattern recognition. Results The content of astragaloside in Astragalus mongholicus (Bge.) Hsiao and A. membranaceus (Fisch.) Bge. was relatively higher than that in the other samples. This is consistent with the Pharmacopoeia of the People's Republic of China in which the two sorts of Astragalus Linn. were regarded as goods. Conclusion This method is a practicable in the quality assessment of Radix Astragali.

The fasting and 2 h levels of glucagon, somatostatin ( SS), and C-peptide during 75 g oral glucose tolerance test in 60 patients with type 2 diabetes and 34 normal subjects were determined. Compared with control group, the fasting levels of glucagon and SS and 2 h levels of SS after glucose loading significantly decreased,while the fasting and 2 h levels of C-peptide increased in diabetes group. The 2 h levels of these hormones were significantly higher than the fasting levels in two groups. Compared with control group, the increased folds of glucagon ( 1.40±0.48 vs 1.20±0. 30, P＜0. 05 ) and SS( 2.79±2. 17 vs 1.14±0. 22, P＜0. 01 ) levels after glucose loading were higher and that of C-peptide level ( 3.58 ±3. 10 vs 8. 33 ± 6. 99, P＜0. 01 ) was lower in diabetes group. The levels of fasting glucagon were positively correlated with that of fasting SS in two groups( both P＜0. 01 ). These results suggest that disturbance exists in hormones from α and δ cells besides the dysfunction of β cells in patients with type 2 diabetes.

Objective? To explore the cutoff points of handgrip strength and its predictive value in frailty assessment in hospitalised patients with cirrhosis. Methods? By convenient sampling, the cirrhosis patients admitted to the Department of Gastroenterology of a ClassⅢ Grade A hospital from March 2017 to April 2018 were selected and studied. Fried frailty phenotype was used as the standard reference, and the receiver operating characteristic curve (ROC) was calculated to determine the best cutoff points of handgrip strength, hence evaluate its predictive value. Results? A total of 80 questionnaires were distributed in which 73 valid ones were retrieved with a effective recovery rate of 91.25%. Among the patients, 40 patients (54.8%) were identified to be at frailty stage and 33 patients (45.2%) were in non-frailty stage; the handgrip strength was (19.72±3.50)kg, which had a negative correlation with age and neutrophil lymphocyte ratio(P＜0.05); at the same time, it was positively correlated with serum albumin and walking speed (P＜ 0.05). The area under the ROC curve of male and female cirrhosis patients was 0.734 and 0.863 respectively, and the optimal cut-off points were 18.95 kg and 15.03 kg; the sensitivity, specificity, positive predictive value and negative predictive value were 95.00%, 81.82%, 86.36%, and 93.10%. Conclusions? When the grip strength of male and female patients were less than or equal to 18.95 kg and 15.03 kg respectively, it indicates that he or she is in a frailty state. Handgrip strength test can be a quick screening tool to identify frailty in inpatients with cirrhosis, and it has high predictive value, and is time-efficient, easy to use, therefore it can be applied in clinical practice.